Go is a heterotrimeric GTP binding protein found predominantly in neural and neuroendocrine tissues and to a lesser extent in heart, fat cells and possibly lung. It appears to transmit signals from a family of receptors to intracellular effectors. In vitro it couples with rhodopsin and alpha2-adrenergic, muscarinic, GABAB, opioid-and f-MetLeuPhe receptors and appears to regulate ion channels. The alpha subunit of Go is a 39 kD polypeptide which binds and hydrolyzes GTP and is ADP-ribosylated by pertussis toxin. Several cDNA clones from a variety of species and tissues were isolated and sequenced. All encoded a protein of 354 amino acids exhibiting a high degree of amino acid homology (98%) among species (Go(alpha)1). Immunologic data, however, were consistent with the hypothesis that there exists another closely related form of Go(alpha). Hybridization of mammalian brain and retinal poly (A)+ RNAs using a bovine Go(alpha)1 cDNA probe showed four major forms of Go(alpha) mRNA ranging in size from 6.2 to 2 kB. Previous studies showed that the 4, 3 and 2 kB forms of Go(alpha) mRNA arise via an alternative splicing mechanism resulting in Go(alpha)1 transcripts which apparently differed only in their 3' untranslated regions (UTRs). Recently, another group isolated and sequenced a new form of Go(alpha) cDNA (Go(alpha)2) from a hamster cDNA library which is completely identical in nucleotide and amino acid sequences to hamster Go(alpha)1 through amino acid 241; it differs in the terminal 3'-coding and -untranslated regions. Two 36-base oligonucleotide probes complementary to analogous regions of the 3' coding regions of Go(alpha)1 and Go(alpha)2 and species-specific 32-base oligonucleotide probes complementary to the 5' UTR of Go(alpha)1 were hybridized to bovine brain and human neuroblastoma poly (A)+ RNA. Results of these studies indicate that the 4, 3 and 2 kB forms are Go(alpha)1-specific mRNAs whereas the 6.2 kB form is the human and bovine equivalent of Go(alpha)2 mRNA. The mechanism by which this new form of Go(alpha) mRNA arises and how it relates to the Go(alpha)1 gene is the subject of our future efforts.